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Negative regulation of the JAK/STAT pathway
Author(s) -
Starr Robyn,
Hilton Douglas J.
Publication year - 1999
Publication title -
bioessays
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.175
H-Index - 184
eISSN - 1521-1878
pISSN - 0265-9247
DOI - 10.1002/(sici)1521-1878(199901)21:1<47::aid-bies6>3.0.co;2-n
Subject(s) - signal transduction , jak stat signaling pathway , stat , microbiology and biotechnology , biology , cytokine receptor , receptor , dephosphorylation , protein tyrosine phosphatase , phosphorylation , kinase , phosphatase , tyrosine kinase , biochemistry , stat3
Cytokines induce a variety of biological responses by binding to specific cell surface receptors and activating cytoplasmic signal transduction pathways, such as the JAK/STAT pathway. Although these responses are generally transient, few molecules have been characterised that switch the signal off. Several different steps of the signal transduction pathway appear to be targeted by negative regulators, including the receptor/ligand complex, JAK kinases, and STAT transcription factors. Negative regulation is achieved by dephosphorylation of signalling intermediates by protein tyrosine phosphatases such as SHP‐1, and by proteolytic degradation. Recent studies have identified two new families of negative regulatory molecules, SOCS and PIAS, which function in novel ways to suppress signal transduction pathways. The duration and intensity of a cell's response to cytokine therefore appear to be determined by the net effect of several regulatory mechanisms. BioEssays 1999;21:47–52. © 1999 John Wiley & Sons, Inc.